Carbocyclizations with substituted alkynes

The [3-1-2] cycloaddition is mostly catalyzed by Ni or Pd catalysts. The MCPs can have substituents on the olefin or cyclopropane, and the two-atom partners can be electron neutral or deficient alkenes, alkynes, and carbon-heteroatom multiple bonds. Since there are different reaction courses of MCP in cycloaddition, introducing substituents on either MCP or the two-atom reaction partners complicates the reaction even more, considering the associated selectivity issues. Consequently, cycloaddition with multi-substituted substrates often gives mixtures though sometimes good selectivity can be achieved by adjusting reaction conditions and substituents. The intramolecular version of [3-1-2] cycloaddition, mainly developed by Motherwell [81], Nakamura [82], Lautens [83], and Mascarenas [87-91], may address the issues of selectivity to some extent, and leads to polycyclic structure meanwhile. AU these have been summarized by several excellent reviews [1, 84—86] and herein we will only update the [3-1-2] cycloaddition of MCP for synthesis of carbocycles with some recent representative examples. 

In a similar way as described for the hydroformylation, the rhodium-catalyzed silaformylation can also be used in a domino process. The elementary step is the formation of an alkenyl-rhodium species by insertion of an alkyne into a Rh-Si bond (silylrhodation), which provides the trigger for a carbocyclization, followed by an insertion of CO. Thus, when Matsuda and coworkers [216] treated a solution of the 1,6-enyne 6/2-87 in benzene with the dimethylphenylsilane under CO pressure (36 kg cm"2) in the presence of catalytic amounts of Rh4(CO)12, the cyclopentane derivative 6/2-88 was obtained in 85 % yield. The procedure is not restricted to the formation of carbocycles rather, heterocycles can also be synthesized using 1,6-enynes as 6/2-89 and 6/2-90 with a heteroatom in the tether (Scheme 6/2.19). Interestingly, 6/2-91 did not lead to the domino product neither could 1,7-enynes be used as substrates, while the Thorpe-Ingold effect (geminal substitution) seems important in achieving good yields. 

In conjunction with this, Jeong reported the cycloadditions of bis(allyl) and bis(homoallyl) acetals of alkynals leading to bicyclic lactols. Smaltz extended its utility to the synthesis of carbocyclic nucleoside by coupling with nucleophilic substitution of a 7r-allylic palladium complex (Equation (46)). ... 

Reaction of enyne-esters and -amides and 2-alkynyl-substituted aromatic ketones in a related fashion led to pyrranylidene complexes (Scheme 8). Compounds with a stabilized anion or a trialkylsilyl enolate in the 4- or 5-position relative to the alkyne can be used in related reactions to give carbocyclic products (Scheme 9). 

Alkenes act as nucleophiles with alkynes in the presence of gold catalysts. In the most simple version of the reaction, enynes are converted with gold complexes or salts, and in the absence of nucleophiles, into rearranged dienes, cyclopropanated carbocycles, and/or bicyclic cyclobutenes. Depending on the length of the tether and the nature of the substituents, the olefin attack to the alkyne occurs in an endo or an exo fashion (equation 33). Besides, substitution at the alkene plays an important role on the regioselectivity of the nucleophilic attack. ... 

The procedure described here illustrates a practical and convenient method for the generation of thio-substituted ketenes which participate in surprisingly facile cycloadditions with both activated and unactivated alkenes, alkynes, and imines to form four-membered carbocycles and heterocycles. As... 

In addition to the preceding processes that involve the preparation of carbocyclic ring systems, [2+2+2] cycloadditions have also been successfully employed with substrates that enable the incorporation of nitrogen and oxygen into the ring formed by cycloaddition. Early studies from Hoberg illustrated the cycloaddition of two alkynes with an isocyanate, and processes of this type have been extensively developed in intramolecular versions to provide access to an array of substituted pyridone derivatives. More recent studies have illustrated that... 

In this field, Cheng et al. have also developed the carbocyclization reaction of aromatic iodides, bicyclic alkenes, and arynes to afford various armulated 9,10-dihydrophenanthrene derivatives 117 (Scheme 12.58) [102]. A related eross-coupling of arynes with aryl iodides but using alkynes as the third component has been described by Larock and Liu, furnishing substituted phenanthrenes 118 (Scheme 12.58) [103]. 

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